A wide variety of tests have been developed for the determination of pregnancy. Commercial early pregnancy determinations generally involve assay of urine or serum. Home pregnancy tests for hCG (human chorionic gonadotropin) in urine include a variety of enzyme immunoassays, hemagglutination inhibition, and antibody-indicator agglutination tests which are effective to indicate pregnancy from 0 to 7 days after a missed period. Confirmation by physician is recommended, particularly to determine abnormal gestation such as ectopic pregnancy.
HCG is produced by the fetal trophoblast and passes from the fetal blood into the mother's blood through the intervillous space in the placenta. HCG levels in maternal blood and urine are often detectable at about 3 weeks. The sensitivity of serum or urine hCG tests is limited because the amount of hCG produced is determined by the amount of trophoblastic tissue, and by dilution of the hCG in the maternal fluids. Until development of the .beta.-hCG specifically binding antibody, cross-reaction with LH (luteinizing hormone) also placed a limit on the level of sensitivity.
We have discovered that normal uterine pregnancies can be reliably determined early in the gestation cycle by testing a sample removed from the vicinity of the cervical canal, cervical os or posterior fornix of the vagina, preferably the external cervical os or posterior fornix, for the presence of fetal restricted antigens, that is, compounds or materials which are produced in the placental tissue and which do not pass in any substantial amounts into the maternal blood. Included in this class of antigens are fetal fibronectins.
We have discovered that ectopic pregnancy can be determined by testing a sample removed from the vicinity of the cervical canal or cervical os for the presence of fetal restricted antigens, that is, compounds or materials which are produced in the placental tissue and which do not pass in any substantial amounts into the maternal blood. Included in this class of materials are fetal fibronectins. If the fetal restricted antigens are substantially depressed in a sample from a person who is tested positive for pregnancy by a blood or urine test for pregnancy, an ectopic pregnancy is indicated.
Determination of the presence of ex vivo products of conception in uterine tissue removed in therapeutic or spontaneous abortion is critically important to confirm the existence of uterine pregnancy and the termination thereof, and to rule out the presence of an ectopic pregnancy. If levels of fetal associated antigens in maternal serum or urine indicate pregnancy, and the uterine tissue removed during a therapeutic abortion does not contain products of conception, a possible ectopic pregnancy is indicated. Presence of products of conception in uterine discharge associated with indicator of spontaneous abortion confirms the abortion, while the absence thereof indicates a continuation of pregnancy. Usual immunoassay techniques for determining the presence of fetal associated antigens in test samples derived from the vaginal cavity are not reliable for indicating the presence of products of conception since these samples typically contain maternal blood. Pregnancy antigens and fetal antigens are usually present in maternal blood as well as in fetal and placental tissue.
Determination of impending preterm births is critical for increasing neonatal survival of preterm infants. Detection of rupture of the amniotic membrane is important in distinguishing true and false labor. When the rupture is small and the volume of amniotic liquid escaping is small, the rupture is often undetected. Accepted methods for detecting ruptured membranes are subjective, not sufficiently sensitive, and not specific. An embodiment of this invention for detection of increased risk of preterm labor and rupture of the amniotic membrane after week 20 of pregnancy is directed to an assay of a test sample removed from the vicinity of the posterior fornix, cervical canal, or cervical os.